Lymphoma, Non-Hodgkin
Conditions
Keywords
Pixantrone, Non-Hodgkins lymphoma
Brief summary
BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and shows reduced potential for cardiotoxicity in animal models. This cytotoxic agent has structural similarities with mitoxantrone as well as general similarities with anthracyclines (such as the tricyclic central quinoid chromophore).
Detailed description
The primary study objective is to compare the efficacy of BBR 2778 to a selection of single agents. Secondary objectives are to compare the safety and tolerability of BBR 2778 to a selection of single agents, and to assess the pharmacokinetic parameters of BBR 2778 in a subset of this patient population.
Interventions
DRUGpixantrone, cyclophosphamide, vincristine, rituximab, prednisone
Day 1: pixantrone (150 mg/m2), cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day)
DRUGVinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab
Day 1: cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day)
Sponsors
CTI BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed aggressive \[de novo or transformed\] NHL according to REAL/WHO classification. * At least one objectively measurable lesion as demonstrated by CT, spiral CT, or MRI and plain radiograph of the chest (chest x-ray, for chest lesions only) that can be followed for response as target lesion. * Relapse after 2 or more prior regimens of chemotherapy * ECOG performance status of 0, 1, or 2 * Adequate hematologic, renal and hepatic function * LVEF ≥50% determined by MUGA scan
Exclusion criteria
* Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m² * Prior allogenic stem cell transplant * Histological diagnosis of Burkitt lymphoma, lymphoblastic lymphoma or Mantle cell lymphoma * Active CNS lymphoma or HIV-related lymphoma. * Any chemotherapy, radiotherapy, or other anticancer treatment (including corticosteroid, 10 or more mg/day of prednisone or equivalent) within the 2 weeks before randomization * Pregnant women or nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) and Complete Response Unconfirmed (CRu) | EOT; approximately 6 months | Proportion of patients with a best response of complete response (CR) or Complete Response unconfirmed (CRu) in the End Of Treatment (EOT) or End Of Study (EOS) analyses by independent assessment in the Intent-to-treat (ITT) population through the End of Treatment (EOT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 18 months after 6 cycles of treatment; approximately 24 months | The time between the date of randomization and the date of the initial documentation of progressive/relapsed disease or death due to any cause. |
| Overall Survival | 18 months after 6 cycles of treatment; approximately 24 months | The time between the date of randomization and the date of death due to any cause. |
| Overall Response Rate (ORR) Lasting at Least 4 Months | approximately 24 months | The proportion of patients with Complete response or Partial Response with a difference from the first documented objective response to disease progression or death of at least 4 months. |
Countries
Argentina, Bulgaria, Costa Rica, Ecuador, Estonia, France, Germany, Hungary, India, Italy, Mexico, Panama, Peru, Poland, Romania, Russia, Ukraine, United Kingdom, United States, Uruguay
Participant flow
Recruitment details
Patients were enrolled from 66 sites: 6 in the U.S, 4 in France, 3 in Bulgaria, 4 sites in Hungary, 3 in Ukraine, 11 in Italy, 2 in Romania, 3 in United Kingdom, 2 in Poland, 2 in Germany, 3 in Peru, 6 in Argentina, 1 in Colombia, 2 in Ecuador, 1 in Uruguay, 5 in Russia and 8 in India.
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle | 70 |
| Comparator Group Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab | 70 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 9 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Patient never treated | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Progressive/Relapsed Disease | 28 | 39 |
| Overall Study | Sponsor decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Comparator Group | Total | Experimental Group |
|---|---|---|---|
| Age, Continuous Age at Randomization (years) | 56.2 years STANDARD_DEVIATION 12.9 | 57.2 years STANDARD_DEVIATION 13.2 | 58.2 years STANDARD_DEVIATION 13.5 |
| Age, Customized 18 to < 30 | 2 Participants | 7 Participants | 5 Participants |
| Age, Customized 30 to < 40 | 9 Participants | 11 Participants | 2 Participants |
| Age, Customized 40 to < 50 | 7 Participants | 16 Participants | 9 Participants |
| Age, Customized 50 to < 60 | 21 Participants | 39 Participants | 18 Participants |
| Age, Customized 60 to < 70 | 21 Participants | 41 Participants | 20 Participants |
| Age, Customized 70 to < 80 | 9 Participants | 24 Participants | 15 Participants |
| Age, Customized ≥ 80 | 1 Participants | 2 Participants | 1 Participants |
| Baseline ECOG Performance Status 0 | 23 Participants | 49 Participants | 26 Participants |
| Baseline ECOG Performance Status 1 | 32 Participants | 62 Participants | 30 Participants |
| Baseline ECOG Performance Status 2 | 14 Participants | 28 Participants | 14 Participants |
| Baseline ECOG Performance Status 3 | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 23 Participants | 10 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 44 Participants | 90 Participants | 46 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 13 Participants | 7 Participants |
| Race/Ethnicity, Customized Native American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 12 Participants | 6 Participants |
| Region of Enrollment Argentina | 5 participants | 11 participants | 6 participants |
| Region of Enrollment Bulgaria | 3 participants | 9 participants | 6 participants |
| Region of Enrollment Colombia | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Ecuador | 4 participants | 7 participants | 3 participants |
| Region of Enrollment France | 4 participants | 8 participants | 4 participants |
| Region of Enrollment Germany | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Hungary | 5 participants | 10 participants | 5 participants |
| Region of Enrollment India | 12 participants | 21 participants | 9 participants |
| Region of Enrollment Italy | 12 participants | 20 participants | 8 participants |
| Region of Enrollment North America | 4 participants | 8 participants | 4 participants |
| Region of Enrollment Peru | 8 participants | 17 participants | 9 participants |
| Region of Enrollment Poland | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Romania | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Russian Federation | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Ukraine | 3 participants | 4 participants | 1 participants |
| Region of Enrollment United Kingdom | 3 participants | 7 participants | 4 participants |
| Region of Enrollment Uruguay | 1 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 30 Participants | 54 Participants | 24 Participants |
| Sex: Female, Male Male | 40 Participants | 86 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 49 / 68 | 52 / 67 |
| other Total, other adverse events | 66 / 68 | 61 / 67 |
| serious Total, serious adverse events | 35 / 68 | 30 / 67 |
Outcome results
Primary
Complete Response (CR) and Complete Response Unconfirmed (CRu)
Proportion of patients with a best response of complete response (CR) or Complete Response unconfirmed (CRu) in the End Of Treatment (EOT) or End Of Study (EOS) analyses by independent assessment in the Intent-to-treat (ITT) population through the End of Treatment (EOT)
Time frame: EOT; approximately 6 months
Population: Intent to Treat (all randomized patients)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental Group | Complete Response (CR) and Complete Response Unconfirmed (CRu) | END OF TREATMENT: CR/CRu, n (%) | 20.0 percentage of randomized patients |
| Experimental Group | Complete Response (CR) and Complete Response Unconfirmed (CRu) | END OF STUDY: CR/CRu, n (%) | 24.3 percentage of randomized patients |
| Comparator Group | Complete Response (CR) and Complete Response Unconfirmed (CRu) | END OF TREATMENT: CR/CRu, n (%) | 5.7 percentage of randomized patients |
| Comparator Group | Complete Response (CR) and Complete Response Unconfirmed (CRu) | END OF STUDY: CR/CRu, n (%) | 7.1 percentage of randomized patients |
Secondary
Overall Response Rate (ORR) Lasting at Least 4 Months
The proportion of patients with Complete response or Partial Response with a difference from the first documented objective response to disease progression or death of at least 4 months.
Time frame: approximately 24 months
Population: Intent-To-Treat (ITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Group | Overall Response Rate (ORR) Lasting at Least 4 Months | 12 participants |
| Comparator Group | Overall Response Rate (ORR) Lasting at Least 4 Months | 6 participants |
Secondary
Overall Survival
The time between the date of randomization and the date of death due to any cause.
Time frame: 18 months after 6 cycles of treatment; approximately 24 months
Population: Intent-To-Treat (ITT) Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group | Overall Survival | 10.2 Months |
| Comparator Group | Overall Survival | 7.6 Months |
Secondary
Progression-Free Survival (PFS)
The time between the date of randomization and the date of the initial documentation of progressive/relapsed disease or death due to any cause.
Time frame: 18 months after 6 cycles of treatment; approximately 24 months
Population: Intent-to-treat patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group | Progression-Free Survival (PFS) | 5.3 months |
| Comparator Group | Progression-Free Survival (PFS) | 2.6 months |